Nondenaturational structural transitions of proteins and biological membranes.

Abstract

This study is concerned with nondenaturational structural rearrangements of proteins in solution under the influence of physiologically moderate temperatures and salts. Temperature-induced rearrangements are viewed as the reason for breaks in Arrhenius curves of the enzymatic activity. In the cytosol as well as in biological membranes, proteins remain conformationally labile and participate in cooperative structural transitions of membranes. Such transitions are initiated by physiologically moderate temperatures, hormones, salts and aminoacids and affect the functional activity of cell membranes. It is suggested that structural lability of proteins and membranes is of importance in metabolic regulation. It may be said without any exaggeration that a basic objective of biochemistry and biophysics is to find the mechanisms by which coordination of numerous chemical and physicochemical processes along with adaptation to a changing environment can be regulated by the cell. An analysis of a large body of accumulated material and information on this subject leads us to a simple idea; namely, that metabolism is regulated primarily through weak physicochemical interactions. It is weak bonds arising at the sites of contact between effector and regulated macromolecules which serve as a trigger for the regulatory mechanisms of various types. This principle is fundamental for the long range mechanism and for the short-range cytoplasmic allosteric enzyme regulation. In each regulatory act of this type the regulated macromolecule undergoes conformational transition between the states of different functional activity. It is generally recognized1,2 that in most cases conformational transition is cooperative by nature. However, biopolymers in a cell are an integral part of compact and orderly membraneous phases with active intermolecular interactions. Therefore it is pertinent to inquire whether the elementary act of regulation is necessarily always restricted to one macromolecule or whether there is a possibility of functionally important cooperative transition involving most if not all components of a polymolecular ensembles. We have in mind here the structural long-range effects when local perturbations in the receptor region of the membrane are able to propagate their effects to comparatively large distances. This would occur in a stepwise cooperative transition between two discrete structural states. After we expressed this idea3,4 we discovered that there had been earlier opinions along such lines5 and in recent years similar views have become widely known6,7,8. Since 1965 our laboratory has been concerned with experimental development of a hypothesis of the membraneous-cooperative-conformational mechanism in the regulation of life processes. We have taken the following path: nondenaturational conformational transitions of proteins in solution → rearrangements at the isolated membrane level → rearrangements in the intact membrane system of the cells.